Trans-activation response element (TAR) | |
---|---|
Identifiers | |
Symbol | mir-TAR |
Alt. Symbols | TAR |
Rfam | RF00250 |
Other data | |
RNA type | Gene; miRNA |
Domain(s) | Viruses |
GO | GO:0035068 GO:0035195 |
SO | SO:0000233 SO:0001244 |
PDB structures | PDBe |
The HIV trans-activation response (TAR) element is an RNA element which is known to be required for the trans-activation of the viral promoter and for virus replication. The TAR hairpin is a dynamic structure [1] that acts as a binding site for the Tat protein, and this interaction stimulates the activity of the long terminal repeat promoter. [2]
Further analysis has shown that TAR is a pre-microRNA that produces mature microRNAs from both strands of the TAR stem-loop. [3] These miRNAs are thought to prevent infected cells from undergoing apoptosis by downregulating the genes ERCC1, IER3, [4] CDK9, and Bim. [5]
Human polyomavirus 2 (JC virus) contains a TAR-homologous sequence in its late promoter [6] that is responsive to HIV-1 derived Tat. [7] [8]
The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.
A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or a retroviral provirus. All retroviral genomes are flanked by LTRs, while there are some retrotransposons without LTRs. Typically, an element flanked by a pair of LTRs will encode a reverse transcriptase and an integrase, allowing the element to be copied and inserted at a different location of the genome. Copies of such an LTR-flanked element can often be found hundreds or thousands of times in a genome. LTR retrotransposons comprise about 8% of the human genome.
The retroviral psi packaging element, also known as the Ψ RNA packaging signal, is a cis-acting RNA element identified in the genomes of the retroviruses Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV). It is involved in regulating the essential process of packaging the retroviral RNA genome into the viral capsid during replication. The final virion contains a dimer of two identical unspliced copies of the viral genome.
Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.
Cyclin-T1 is a protein that in humans is encoded by the CCNT1 gene.
DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene.
Transcription factor RelB is a protein that in humans is encoded by the RELB gene.
DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene.
DNA-directed RNA polymerase II subunit RPB11-a is an enzyme that in humans is encoded by the POLR2J gene.
DNA-directed RNA polymerases I, II, and III subunit RPABC4 is a protein that in humans is encoded by the POLR2K gene.
DNA-directed RNA polymerase II subunit RPB4 is an enzyme that in humans is encoded by the POLR2D gene.
Pur-alpha is a protein that in humans is encoded by the PURA gene located at chromosome 5, band q31.
Transcription initiation factor TFIID subunit 7 also known as TAFII55 is a protein that in humans is encoded by the TAF7 gene.
HIV Tat-specific factor 1 is a protein that in humans is encoded by the HTATSF1 gene.
RISC-loading complex subunit TARBP2 is a protein that in humans is encoded by the TARBP2 gene.
Probable methyltransferase TARBP1 is an enzyme that in humans is encoded by the TARBP1 gene.
In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.
Rev is a transactivating protein that is essential to the regulation of HIV-1 protein expression. A nuclear localization signal is encoded in the rev gene, which allows the Rev protein to be localized to the nucleus, where it is involved in the export of unspliced and incompletely spliced mRNAs. In the absence of Rev, mRNAs of the HIV-1 late (structural) genes are retained in the nucleus, preventing their translation.
In genetics, a kissing stem-loop, or kissing stem loop interaction, is formed in ribonucleic acid (RNA) when two bases between two hairpin loops pair. These intra- and intermolecular kissing interactions are important in forming the tertiary or quaternary structure of many RNAs.
Human Immunodeficiency Virus (HIV) has the capability to enter a latent stage of infection where it exists as a dormant provirus in CD4+ T-cells. Most latently infected cells are resting memory T cells, however a small fraction of latently infected cells isolated from HIV patients are naive CD4 T cells.